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Fluoroquinolone resistance in Streptococcus pneumoniae isolates in Germany from 2004-2005 to 2014-2015
Julia Schmitz1, Mark van der Linden1, Adnan Al-Lahham2
1Institute of Medical Microbiology, National Reference Center for Streptococci, University Hospital (RWTH), Aachen, Germany.
Abstract:
Streptococcus pneumoniae is a major cause of bacterial pneumonia, sepsis and meningitis worldwide. Prevalence of levofloxacin-resistant S. pneumoniae isolates in Germany and associated mutations in the quinolone resistance determining regions (QRDRs), as well as serotype distribution and multi locus sequence types (MLST) are shown. 21,764 invasive S. pneumoniae isolates from Germany, isolated in the epidemiological seasons from 2004/05 to 2014/15 were analyzed at the German National Reference Centre for Streptococci (GNRCS) for their levofloxacin resistance by micro broth dilution method. All resistant (minimal inhibitory concentration (MIC) ≥8μg/ml) and intermediate (MIC >2μg/ml and <8μg/ml) isolates were selected for the present study. Additionally, 29 susceptible isolates were randomly selected. A total of ninety isolates were tested for their levofloxacin-MIC by Etest, their serotype and sequence type, as well as for point-mutations at the QRDRs in the genes parC, parE, gyrA and gyrB. Twenty-five isolates exhibited levofloxacin MICs <2μg/ml (Etest) and no mutations in the QRDRs. Four isolates with MICs=2μg/ml had one mutation in parC; isolates with MICs >2μg/ml all had one or more mutations in the QRDRs. Four of nine intermediate isolates had a mutation in either parC or gyrA, and four isolates had mutations in both parC and gyrB. One isolate had mutations in both parC and gyrA. All isolates with MICs ≥8μg/ml (52) had mutations in both topoisomerase IV and gyrase. Serotypes associated with levofloxacin resistance shifted from a majority of PCV13 serotypes before the introduction of the PCV13 vaccine towards non-PCV serotypes. Resistant isolates were almost exclusively found among adults (98.1%).
Insights
Levofloxacin resistance in Streptococcus pneumoniae is linked to specific mutations in QRDRs, particularly in adults. Serotype distribution also shifted post-PCV13 vaccine introduction.
Area of Science:
- Microbiology
- Molecular Biology
- Epidemiology
Background:
- Streptococcus pneumoniae causes significant global morbidity and mortality from pneumonia, sepsis, and meningitis.
- Understanding antimicrobial resistance patterns, such as levofloxacin resistance, is crucial for effective treatment strategies.
- The quinolone resistance determining regions (QRDRs) in bacterial genes are key sites for mutations conferring antibiotic resistance.
Purpose of the Study:
- To investigate the prevalence of levofloxacin-resistant Streptococcus pneumoniae in Germany.
- To identify specific mutations in QRDRs associated with levofloxacin resistance.
- To analyze serotype distribution and multi locus sequence types (MLST) in resistant isolates.
Main Methods:
- Analysis of 21,764 invasive S. pneumoniae isolates from Germany (2004/05-2014/15).
- Levofloxacin resistance testing using micro broth dilution and Etest.
- Genomic analysis for point mutations in parC, parE, gyrA, and gyrB genes (QRDRs).
- Serotyping and MLST for characterizing resistant isolates.
Main Results:
- All levofloxacin-resistant isolates (MIC ≥8μg/ml) possessed mutations in both topoisomerase IV and gyrase genes.
- Intermediate resistance (MIC >2μg/ml) was associated with mutations in parC, gyrA, or gyrB.
- A shift in serotypes associated with resistance was observed, moving from PCV13 serotypes to non-PCV serotypes after PCV13 vaccine introduction.
- Resistant isolates were predominantly found in adults (98.1%).
Conclusions:
- Levofloxacin resistance in S. pneumoniae is strongly correlated with specific QRDR mutations.
- The emergence and spread of resistant strains are influenced by vaccination strategies and patient demographics.
- Continued surveillance of resistance mechanisms and serotype epidemiology is essential.
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